During this period, the research team has conducted a high-throughput biochemical screen of NCATS small molecule libraries. The identified hits will be cherrypicked, validated and counterscreened for specificity against other closely-related USPs. Based on these compound activity profiles, a medicinal chemistry campaign will be initiated for the most promising chemotypes and lead compounds will be evaluated in relevant models/assays of Downs syndrome and degenerative diseases, including in vivo assays (such as learning glucose intolerance and bone density).